The COVID-19 epidemic that occurred at the end of 2019 spreads rapidly to all parts of the world, putting the global public health system to a severe test. With the continuation of the epidemic, SARS-CoV-2 variants are constantly emerging. In particular, the mutation of the spike protein can cause changes in the infectivity and antigenicity of the virus, resulting in an increase in the infectivity and a decline in the protective efficacy of existing vaccines, and even the replacement of epidemic strains. This is also one of the reasons why the epidemic has not been effectively controlled so far. Nowadays, the main circulating variants have changed their characteristics to a certain extent, and the neutralization sensitivity of some variants to neutralizing monoclonal antibodies, immune sera and convalescent sera has decreased to a certain extent compared with the original strains. The emergence of variants is not only related to the characteristics of the virus itself, but also to the changes of transmission host and the chronic infection in people with deficient immunity. The emerging variants should be closely monitored, and their functional characteristics should be systematically studied so as to provide data for vaccine research and development and the designation of immunization strategies.

Tertiary lymphoid structure (TLS) is the ectopic lymphoid tissue around the chronic inflammatory site of tumor, infection diseases, autoimmunity diseases, organ transplantation and so on. TLS is regarded as the vital niche of antitumor immune response in tumor microenvironment for abundant immune cells, and is correlated with better clinical outcomes and immunotherapy response in most solid tumors. As a typical inflammation-driven cancer, hepatocellular carcinoma (HCC) is controversial with the influence of TLS on patients prognosis. In this paper, the composition, formation mechanism, recognition and clinical value of TLS in HCC were briefly reviewed.

Objective:To investigate the use of different tools of intravenous infusion and the issues associated with intravenous catheter indwelling in hospitalized children and to provide reference for clinical practices.Methods:Using the convenient sampling method, from July 24th to 31st, 2018, the intravenous infusion treatment of children inpatients in 49 hospitals within the Beijing Children's Hospital Medical Association was selected for investigation. A self-designed Cross-sectional Questionnaire for Children's Intravenous Infusion and a photo of an intravenous infusion tool were used for data collection. Statistical analysis was performed using SPSS 17.0 software.Results:During the data collection period, there were 18 316 hospitalized children in the 49 hospitals, among which there were 14 421 cases of infusions, with the infusions rate of 78.73%. The application rate of indwelling needle was 87.94%. The connector of venous catheter was mainly heparin cap connection (64.23%) . The infusion tools used in 6 398 cases (44.37%) were made by PVC and containing 2-ethyl hexyl phthalate (DEHP) . Aseptic transparent dressing was the main dressing choice. During catheter indwelling, there were some problems such as back-blood in the pipeline or infusion joint, incorrect clamping position of small clips, unclamping, and tube detachment. Indwelling needles had more problems than central venous catheters, including old blood returning in the tube and blood returning in the infusion connector. The difference between the peripheral indwelling needle and the central catheter was statistically significant ( P<0.05) . Conclusions:The rate of intravenous infusion in hospitalized children is relatively high. Although there are various types of intravenous infusion tools, the choice of infusion tools for children was mainly indwelling needle and heparin cap connection, and there were still room for improvement in catheter maintenance.

Objective: To make a preliminary assessment on the immunogenicity of a quadrivalence recombinant human papillomavirus (HPV) vaccine (6, 11, 16 and 18 types) (Hansenulapolymorpha) in healthy women aged 18-45 years in phaseⅠclinical study. Methods: It was a single-center, double-blind, randomized, placebo-controlled phaseⅠ clinical study. Women aged 18-45 years were randomized (2∶1) to receive HPV vaccine (n=60) or placebo control (n=30) at months 0, 2 and 6. Antibodies against HPV6/11/16/18 were detected by pseudovirus-based neutralisation assay in serum samples collected at 0 d, 180 d and 210 d. Seroconversion rates and geometric mean titres (GMT) of antibodies against the four types of antigens were calculated. Results: Seroconversion rates of the vaccination group at 180 d (before the third dose) and 210 d (one month after the third dose) were generally similar and between 85%-100% for all types of antibodies. The GMT of antibodies at one month after the last dose improved significantly compared with those before immunization. Conclusions These results showed that the HPV vaccine had good immunogenicity in the population of healthy women aged 18-45 years. Higher antibody titers were elicited by the vaccine compare with the tites before the first dose and in the placebo control group.

Objective: To validate a pseudovirus-based neutralization assay for the detection of antibodies against human papillomavirus (HPV) in human serum samples. Methods: The specificity, accuracy, precision, range of linearity, limit of detection and robustness of the neutralization assay were evaluated using HPV-negative serum samples, vaccinated serum samples with quadri-valent vaccine, and international standards for detecting antibodies against HPV16 and HPV18. Results: Based on the data of the HPV-naïve samples, the criteria of positivity was determined as follows: the 50% inhibitory dose (ID₅₀) of the tested sample was not less than 40 and 2-fold not less than that for bovine papillomavirus. The neutralization assay showed good accuracy with a recovery rate of 87%-122% and excellent reproducibility with intra- and inter-assay variation of 5%-27% and 10%-26% respectively. The HPV16 and HPV18 international standards were used to define the limit of quantification, which was 1.28 IU/ml for HPV16 and 0.96 IU/ml for HPV18. Acceptable ranges of variation for the key parameters of this assay were defined, which showed the good robustness of the pseudovirus-based neutralization assay. Conclusion The pseudovirus-based neutralization assay for the detection of HPV antibodies showed good specificity, accuracy, sensitivity, and robustness, suggesting that it could be used to evaluate the immunogenicity of HPV vaccines.

Cervical cancer is the second most common cancer in women worldwide. It is clear that persistent infection of high-risk human papillomaviruses (HR-HPVs) is the main cause for this disease. Among the several HPV types associated with carcinoma, HPV-16 is the most prevalent type and present in about 50% of tumor specimens. The major capsid protein (L1) of HPV can self-assemble into virus-like particles (VLPs) with immunogenicity similar to infectious virions. Neutralizing epitopes are the structural basis of the current prophylactic HPV vaccines. The efficacy of HPV vaccines is critically dependent upon the integrity of type-specific neutralizing epitopes. Recently, considerable headway has been made in studying the epitopes of HPV16 based on neutralizing antibodies. Notably, more and more HPV16 variants have appeared along with increasing immune pressure. To study the phenotypic variations in HPV16 L1 protein, 1 204 naturally occurring sequences were analyzed and a phylogenetic tree was then constructed including four clades. Moreover, after compared the aforementioned sequences with the 114K reference sequence, eight "hot mutation sites" , six "specialized mutation sites" and 20 "epitope-related mutation sites" were found. Generally, sera raised against VLPs can neutralize the corresponding HPV types, but not other types. However, it is not known whether intragenotypic variants of human papillomavirus type 16 (HPV-16) can be neutralized by sera vaccinated with a single variant VLPs. It is, therefore, imperative to understand the neutralizing epitopes and intragenotypic variants of HPV-16 for the production of prophylactic vaccines with high potency and broad coverage.

Human papillomavirus (HPV) infection is the most common sex-transmitted virus infection. Persistent infection of HPV could cause cancers in different parts of the body, such as cervix and anus. Up to now, three prophylactic HPV vaccines have been approved to prevent HPV infection and related diseases. It is well accepted that neutralizing antibodies are the mediator of protection. Analysis of immunogenicity has been playing a key role in HPV vaccine clinical trials, especially in the evaluation of durability of immune responses, immunobridging in young girls and boys, and reduced-dose schedules. There is still no unique method for the evaluation of immunogenicity of HPV vaccines in clinical trials. The data of immunogenicity from different clinical trials cannot be compared directly. It is urgently needed to establish a high throughput and protection-related unique assay as well as standard materials for its standardization. To accelerate the development and evaluation of prophylactic HPV vaccines, a standardized method should be well validated and transferred to different laboratories to make clinical immunogenicity data comparable.

BACKGROUND:Delayed graft function (DGF) occurs frequently in kidney transplants from donation after cardiac death if creatinine level is high in kidney recipients. OBJECTIVE:To analyze the clinical effects of renal transplantation with kidneys from donors dying of cardiac death in organophosphate poisoning. METHODS:Data were col ected from kidney transplants from two donors dying of cardiac death in organophosphate poisoning. After some donor maintenance, donor organ were obtained and perfused with impulse type machine. Recipients were treated with intervention of immunity induction, anti-rejection drugs and infection prevention drugs during and after renal transplantation. Pathological data of donor kidney zero needle biopsy, DGF after kidney transplantation, complication rate (such as acute rejection), renal al ograft recovery situation, the survival rate of recipients and kidney transplants were col ected and analyzed. RESULTS AND CONCLUSION:Needle biopsy results from four donor kidneys showed that glomerular morphology was normal, but there were edema and degeneration in kidney tubules in some degree. Donor DGF rate was 75%(3/4), acute rejection rate was 0%(0/4), perioperative period donor kidney and recipient survival rate were 100%(4/4). Al recipients showed a good result of transplanted kidney, their creatinine and urea nitrogen were at low level, and had no proteinuria. One recipient died of severe pulmonary infection 4 months after surgery. For some organophosphate poisoning donors dying of cardiac death, donor kidney quality can be improved by suitable donor maintenance and high-quality donor kidney preservation using machine perfusion. Kidney transplants from donors dying of cardiac death in organophosphate poisoning who receive the maintenance of organ function may be a promising candidate for renal transplantation due to a severe lack of kidney donor sources.

OBJECTIVETo study the clinical and histopathologic features of post-transplant kidney biopsy tissues from pediatric C-III donors.

METHODSThe clinical and pathologic features of 20 cases (22 case-times) of renal transplant biopsies from pediatric cadaveric donors were analyzed by light microscopy and immunohistochemistry according to the Banff system of working classification of renal allograft pathology. Biopsies were compared to those from adult C-III donors and adult cadaveric donors.

RESULTSSixteen cases (72.7%) showed renal allograft drug toxicity damage by Tacrolimus, seven cases (31.8%) showed degeneration and necrosis of renal tubular epithelial cells, four cases (18.2%) showed T cell-mediated acute rejection and six cases (27.3%) showed renal interstitial inflammation. There were two cases (9.1%) of renal dysplasia and one case (4.5%) of renal infarction. There was insufficient evidence for diagnosis of renal allograft nephropathy. Compared to post-transplant kidney from adult C-III donors, the proportion of drug toxicity damage was higher (P<0.05). Compared to post-transplant kidney from adult cadavers, the proportions of drug toxicity damage, degeneration and necrosis of renal tubular epithelial cells were higher (P<0.05) while the proportion of acute rejection was lower (P<0.05).

CONCLUSIONSThe pathologic changes in the post-transplant kidneys from pediatric donors are different from those from adult donors. Optimal long-term outcome can be accomplished by effective treatment based on timely or procedural biopsy.

Adult ; Age Factors ; Biopsy ; Cadaver ; Child ; Graft Rejection ; pathology ; Humans ; Immunohistochemistry ; Immunosuppressive Agents ; adverse effects ; Infarction ; pathology ; Kidney ; blood supply ; drug effects ; pathology ; Kidney Transplantation ; Kidney Tubules ; drug effects ; pathology ; Necrosis ; Tacrolimus ; adverse effects ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo observe the effects of acupuncture-moxibustion on chronic allograft nephropathy (CAN) and explore the methods of acupoint selection along meridian for transplanted-kidney-related diseases.

METHODSA total of 180 patients of CAN were randomized into a syndrome differentiation group, a spleen-meridian group, a kidney-meridian group and a control group, 45 cases in each one. A total of 33 cases dropped out before the end of the study, including 8 cases in the syndrome differentiation group, 12 cases in the spleen-meridian group, 13 cases in the kidney-meridian group and no case in the control group. Patients in the control group were treated with conventional western medicine; based on this, patients in other three groups were treated with acupuncture-moxibustion. In the syndrome differentiation group, Qihai (CV 6), Hegu (LI 4), Guanyuan (CV 4), Feishu (BL 13), Shenshu (BL 23), etc. were selected for qi deficiency of lung and kidney; Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Yinlingquan (SP 9), etc. were selected for deficiency of qi and yin; Ganshu (BL 18), Shenshu (BL 23), Sanyinjiao (SP 6), Taixi (KI 3), Yinlingquan (SP 9), Ququan (LR 8), etc. were selected for yin deficiency of liver and kidney; Zhongji (CV 3), Guanyuan (CV 4), Mingmen (GV 4), Guanyuanshu (BL 26), etc. were selected for yang deficiency of spleen and kidney. In addition, Sanyinjiao (SP 6), Diji (SP 8), Yinlingquan (SP 9), Xuehai (SP 10), etc. were added in the spleen-meridian group; Taixi (KI 3), Zhaohai (KI 6), Fuliu (KI 7), Ciliao (BL 32), etc: were added in the kidney-meridian group. Serum creatinine (Scr), creatinine clearance (Ccr) and 24-hour urinary protein before and after the treatment were com- pared among the four groups.

RESULTSAfter treatment, 24-hour urinary protein in the acupuncture-moxibustion groups and control group were all reduced (all P < 0.05); compared before treatment, the Scr in the spleen-meridian group was significantly reduced (P < 0.05); the difference of Ccr before and after treatment was insignificant in all the groups (all P > 0.05). Compared with the control group, 24-hour urinary protein in spleen-meridian group could relieve or recover the damage of transplant kidney induced by CAN. A new interlink may be established between the transplanted kidneys and the spleen meridians, indicating that transplanted kidney-related diseases can be treated by selecting acupoints of spleen meridian.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Allografts ; physiopathology ; Female ; Graft Rejection ; Humans ; Kidney Transplantation ; adverse effects ; Male ; Meridians ; Middle Aged ; Moxibustion ; Renal Insufficiency, Chronic ; etiology ; therapy ; Transplantation, Homologous ; adverse effects